Endoscopic Endonasal Approach is Superior to Transcranial Approach for Small to Medium Tuberculum Sellae Meningiomas in Terms of Visual Outcome and Complications: A Retrospective Study in a Single Center.

OBJECTIVE: This study compared the effectiveness of the endoscopic endonasal approach (EEA) versus the conventional transcranial approach (TCA) for treating tuberculum sellae meningiomas (TSMs), aiming to identify the superior surgical method and risk factors affecting outcomes. METHODS: A retrospective analysis was conducted on patients treated for TSM from 1998 to 2023 at our institution, evaluating patient characteristics, tumor features, outcomes, and complications. A novel grading system for preoperative evaluation of TSMs was also proposed. RESULTS: Among 49 patients, 26 underwent EEA and 23 TCA. The maximum diameters were comparable between the groups (mean, 22 mm vs. 23 mm, respectively). The gross total resection (GTR) rates were 62% for EEA and 70% for TCA, showing no significant difference. However, post-surgical visual improvement was significantly higher in the EEA group compared to the TCA group (77% vs. 44%; p = 0.020), with fewer complications in the EEA group (8% vs. 35%; p = 0.032). CONCLUSION: EEA offers a safe and effective treatment for small to medium TSMs, with outcomes comparable to TCA in terms of resection but superior in visual improvement and fewer complications. Surgical approach selection should consider patient and tumor characteristics, along with surgeon experience.

Role of intraoperative ultrasound and MRI to aid grade of resection of pediatric low-grade gliomas: accumulated experience from 4 centers.

PURPOSE: Pediatric low-grade gliomas (pLGG) are the most common brain tumors in children and achieving complete resection (CR) in pLGG is the most important prognostic factor. There are multiple intraoperative tools to optimize the extent of resection (EOR). This article investigates and discusses the role of intraoperative ultrasound (iUS) and intraoperative magnetic resonance imaging (iMRI) in the surgical treatment of pLGG. METHODS: The tumor registries at Tuebingen, Rome and Pretoria were searched for pLGG with the use of iUS and data on EOR. The tumor registries at Liverpool and Tuebingen were searched for pLGG with the use of iMRI where preoperative CR was the surgical intent. Different iUS and iMRI machines were used in the 4 centers. RESULTS: We included 111 operations which used iUS and 182 operations using iMRI. Both modalities facilitated intended CR in hemispheric supra- and infratentorial location in almost all cases. In more deep-seated tumor location like supratentorial midline tumors, iMRI has advantages over iUS to visualize residual tumor. Functional limitations limiting CR arising from eloquent involved or neighboring brain tissue apply to both modalities in the same way. In the long-term follow-up, both iUS and iMRI show that achieving a complete resection on intraoperative imaging significantly lowers recurrence of disease (chi-square test, p < 0.01). CONCLUSION: iUS and iMRI have specific pros and cons, but both have been proven to improve achieving CR in pLGG. Due to advances in image quality, cost- and time-efficiency, and efforts to improve the user interface, iUS has emerged as the most accessible surgical adjunct to date to aid and guide tumor resection. Since the EOR has the most important effect on long-term outcome and disease control of pLGG in most locations, we strongly recommend taking all possible efforts to use iUS in any surgery, independent of intended resection extent and iMRI if locally available.

Long-term outcomes of CNS WHO grade 2 oligodendroglioma in adult patients: a single-institution experience.

PURPOSE: Oligodendrogliomas (ODGs) are a subtype of diffuse lower-grade gliomas with overall survival of > 10 years. This study aims to analyze long-term outcomes and identify prognostic factors in patients with WHO grade 2 ODG. METHODS: We retrospectively reviewed 138 adult patients diagnosed with 1p/19q co-deleted ODG who underwent surgical resection or biopsy between 1994 and 2021, analyzing clinical data, treatment details, and outcomes. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier analysis. Univariate and multivariate Cox regression analyses were utilized to identify significant prognostic factors. RESULTS: In the gross total resection (GTR) group, 63 (45.7%) underwent observation and 5 (3.6%) received postoperative treatment; in the non-GTR group, 37 (26.8%) were observed and 33 (23.9%) received postoperative treatment. The median PFS and OS were 6.8 and 18.4 years, respectively. Between adjuvant treatment and observation, there was no significant difference in PFS or OS. However, GTR or STR with less than 10% residual tumor exhibited significantly better PFS and OS compared to PR or biopsy (p = 0.022 and 0.032, respectively). Multivariate analysis revealed that contrast enhancement on MRI was associated with worse PFS (HR = 2.36, p < 0.001) and OS (HR = 5.89, p = 0.001). And the presence of seizures at presentation was associated with improved OS (HR = 0.28, p = 0.006). CONCLUSION: This study underscores favorable long-term outcomes for patients with 1p/19q co-deleted ODG WHO grade 2. Our findings indicate that the EOR plays a crucial role as a significant prognostic factor in enhancing PFS and OS outcomes in WHO grade 2 ODG.

Surgical treatment for insular gliomas. A systematic review and meta-analysis on behalf of the EANS neuro-oncology section.

Introduction: The appropriate surgical management of insular gliomas is controversial. Management strategies vary considerably between centers. Research question: To provide robust resection, functional and epilepsy outcome figures, study growth patterns and tumor classification paradigms, analyze surgical approaches, mapping/monitoring strategies, surgery for insular glioblastoma, as well as molecular findings, and to identify open questions for future research. Material and methods: On behalf of the EANS Neuro-oncology Section we performed a systematic review and meta-analysis (using a random-effects model) of the more current (2000-2023) literature in accordance with the PRISMA guidelines. Results: The pooled postoperative motor and speech deficit rates were 6.8% and 3.6%. There was a 79.6% chance for postoperative epilepsy control. The postoperative KPI was 80-100 in 83.5% of cases. Functional monitoring/mapping paradigms (which may include awake craniotomies) seem mandatory. (Additional) awake surgery may result in slightly better functional but also worse resection outcomes. Transcortical approaches may carry a lesser rate of (motor) deficits than transsylvian surgeries. Discussion and conclusions: This paper provides an inclusive overview and analysis of current surgical management of insular gliomas. Risks and complication rates in experienced centers do not necessarily compare unfavorably with the results of routine neuro-oncological procedures. Limitations of the current literature prominently include a lack of standardized outcome reporting. Questions and issues that warrant more attention include surgery for insular glioblastomas and how to classify the various growth patterns of insular gliomas.

Factors affecting the extent of resection and neurological outcomes following transopercular resection of insular gliomas.

BACKGROUND: Surgical resection of insular gliomas is a challenge. TO resection is considered more versatile and has lower risk of vascular damage. In this study, we aimed to understand the factors that affect resection rates, ischemic changes and neurological outcomes and studied the utility of IONM in patients who underwent TO resection for IGs. METHODS: Retrospective analysis of 66 patients with IG who underwent TO resection was performed. RESULTS: Radical resection was possible in 39% patients. Involvement of zone II and the absence of contrast enhancement predicted lower resection rate. Persistent deficit rate was 10.9%. Although dominant lobe tumors increased immediate deficit and fronto-orbital operculum involvement reduced prolonged deficit rate, no tumor related factor showed significant association with persistent deficits. 45% of patients developed a postoperative infarct, 53% of whom developed deficits. Most affected vascular territory was lenticulostriate (39%). MEP changes were observed in 9/57 patients. 67% of stable TcMEPs and 74.5% of stable strip MEPs did not develop any postoperative motor deficits. Long-term deficits were seen in 3 and 6% patients with stable TcMEP and strip MEPs respectively. In contrast, 25% and 50% of patients with reversible strip MEP and Tc MEP changes respectively had persistent motor deficits. DWI changes were clinically more relevant when accompanied by MEP changes intraoperatively, with persistent deficit rates three times greater when MEP changes occurred than when MEPs were stable. CONCLUSION: Radical resection can be achieved in large, multizone IGs, with reasonable outcomes using TO approach and multimodal intraoperative strategy with IONM.

Standardized evaluation of the extent of resection in glioblastoma with automated early post-operative segmentation.

Standard treatment of patients with glioblastoma includes surgical resection of the tumor. The extent of resection (EOR) achieved during surgery significantly impacts prognosis and is used to stratify patients in clinical trials. In this study, we developed a U-Net-based deep-learning model to segment contrast-enhancing tumor on post-operative MRI exams taken within 72 h of resection surgery and used these segmentations to classify the EOR as either maximal or submaximal. The model was trained on 122 multiparametric MRI scans from our institution and achieved a mean Dice score of 0.52 ± 0.03 on an external dataset (n = 248), a performance -on par with the interrater agreement between expert annotators as reported in literature. We obtained an EOR classification precision/recall of 0.72/0.78 on the internal test dataset (n = 462) and 0.90/0.87 on the external dataset. Furthermore, Kaplan-Meier curves were used to compare the overall survival between patients with maximal and submaximal resection in the internal test dataset, as determined by either clinicians or the model. There was no significant difference between the survival predictions using the model's and clinical EOR classification. We find that the proposed segmentation model is capable of reliably classifying the EOR of glioblastoma tumors on early post-operative MRI scans. Moreover, we show that stratification of patients based on the model's predictions offers at least the same prognostic value as when done by clinicians.

Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

Adaption of neurosurgical resection patterns for pediatric low-grade glioma spanning two decades-Report from the German LGG-studies 1996-2018.

INTRODUCTION: Neurosurgery is considered the mainstay of treatment for pediatric low-grade glioma (LGG); the extent of resection determines subsequent stratification in current treatment protocols. Yet, surgical radicality must be balanced against the risks of complications that may affect long-term quality of life. We investigated whether this consideration impacted surgical resection patterns over time for patients of the German LGG studies. PATIENTS AND METHODS: Four thousand two hundred and seventy pediatric patients from three successive LGG studies (median age at diagnosis 7.6 years, neurofibromatosis (NF1) 14.7%) were grouped into 5 consecutive time intervals (TI1-5) for date of diagnosis and analyzed for timing and extent of first surgery with respect to tumor site, histology, NF1-status, sex, and age. RESULTS: The fraction of radiological LGG diagnoses increased over time (TI1 12.6%; TI5 21.7%), while the extent of the first neurosurgical intervention (3440/4270) showed a reduced fraction of complete/subtotal and an increase of partial resections from TI1 to TI5. Binary logistic regression analysis for the first intervention within the first year following diagnosis confirmed the temporal trends (p < 0.001) and the link with tumor site for each extent of resection (p < 0.001). Higher age is related to more complete resections in the cerebellum and cerebral hemispheres. CONCLUSIONS: The declining extent of surgical resections over time was unrelated to patient characteristics. It paralleled the evolution of comprehensive treatment algorithms; thus, it may reflect alignment of surgical practice to recommendations in respect to age, tumor site, and NF1-status integrated as such into current treatment guidelines. Further investigations are needed to understand how planning, performance, or tumor characteristics impact achieving surgical goals.

Clinical and molecular features of patients with IDH1 wild-type primary glioblastoma presenting unexpected short-term survival after gross total resection.

BACKGROUND: This study investigated the factors influencing short-term survivors (STS) after gross total resection (GTR) in patients with IDH1 wild-type primary glioblastoma. METHODS: We analyzed five independent cohorts who underwent GTR, including 83 patients from Kitasato University (K-cohort), and four validation cohorts of 148 patients from co-investigators (V-cohort), 66 patients from the Kansai Molecular Diagnosis Network for the Central Nervous System tumors, 109 patients from the Cancer Genome Atlas, and 40 patients from the Glioma Longitudinal AnalySiS. The study defined STS as those who had an overall survival ≤ 12 months after GTR with subsequent radiation therapy, and concurrent and adjuvant temozolomide (TMZ). RESULTS: The study included 446 patients with glioblastoma. All cohorts experienced unexpected STS after GTR, with a range of 15.0-23.9% of the cases. Molecular profiling revealed no significant difference in major genetic alterations between the STS and non-STS groups, including MGMT, TERT, EGFR, PTEN, and CDKN2A. Clinically, the STS group had a higher incidence of non-local recurrence early in their treatment course, with 60.0% of non-local recurrence in the K-cohort and 43.5% in the V-cohort. CONCLUSIONS: The study revealed that unexpected STS after GTR in patients with glioblastoma is not uncommon and such tumors tend to present early non-local recurrence. Interestingly, we did not find any significant genetic alterations in the STS group, indicating that such major alterations are characteristics of GB rather than being reliable predictors for recurrence patterns or development of unexpected STS.

Surgical Management of High-Grade Meningiomas.

Maximal resection with the preservation of neurological function are the mainstays of the surgical management of high-grade meningiomas. Surgical morbidity is strongly associated with tumor size, location, and invasiveness, whereas patient survival is strongly associated with the extent of resection, tumor biology, and patient health. A versatile microsurgical skill set combined with a cogent multimodality treatment plan is critical in order to achieve optimal patient outcomes. Continued refinement in surgical techniques in conjunction with directed radiotherapeutic and medical therapies will define future treatment.

Application of Delta T1 maps for quantitative and objective assessment of extent of resection and survival prediction in glioblastoma.

Background and Objectives: Gross-total resection (GTR) and low residual tumor volume (RTV) have been associated with increased survival in glioblastoma. Largely due to the subjectivity involved, the determination of GTR and RTV remains difficult in the postoperative setting. In response, the objective of this study is to evaluate the clinical efficacy of an easy-to-use MRI metric, called delta T1 (dT1), to quantify extent of resection (EOR) and RTV, in comparison to radiologist impression, to predict overall survival (OS) in glioblastoma patients. Methods: 59 patients who underwent resection of glioblastoma were retrospectively identified. Delta T1 (dT1) images, automatically created from the difference between calibrated post- and pre-contrast T1-weighted images, were used to quantify EOR and RTV. Kaplan-Meier survival estimates were determined for EOR categories, an RTV cutoff of 5cm3 and radiologist interpretation of EOR. Multivariate Cox proportional hazard regression analysis was used to evaluate RTV and EOR along with effects related to sex, KPS, MGMT, and age on OS. Results: Kaplan-Meier analysis revealed a statistically significant difference in median OS for a dT1-determined RTV cutoff of 5 cm3 (P=.0024, HR=2.18 (1.232-3.856)), but not for radiological impression (P=0.666) or dT1-determined EOR (P=0.0803), which was limited to a comparison between partial and subtotal resections. Furthermore, when covariates were accounted for in multivariate Cox regression, significant differences in OS were retained for dT1-determined RTV. Additionally, a significantly strong yet short-term effect of MGMT methylation status on OS was revealed for each RTV and EOR model. Conclusion: The utility of dT1 maps to quantify EOR and RTV in glioblastoma and predict survival, suggests an emerging role for dT1s with relevance for intraoperative MRI, neuro-navigation and postoperative disease surveillance.

Long-term outcome of primary clival chordomas: a single-center retrospective study with an emphasis on the timing of recurrences based on the primary treatment.

OBJECTIVE: This study aimed to provide data on extended outcomes in primary clival chordomas, focusing on progression-free survival (PFS) and overall survival (OS). METHODS: A retrospective single-center analysis was conducted on patients with clival chordoma treated between 1987 and 2022 using surgery, stereotactic radiosurgery, or proton radiation therapy (PRT). RESULTS: The study included 100 patients (median age 44 years, 51% male). Surgery was performed using the endoscopic endonasal approach in 71 patients (71%). Gross-total resection (GTR) or near-total resection (NTR) was attained in 39 patients (39%). Postoperatively, new cranial nerve deficits occurred in 7%, CSF leak in 4%, and meningitis in none of the patients. Radiation therapy was performed in 79 patients (79%), with PRT in 50 patients (50%) as the primary treatment. During the median follow-up period of 73 (interquartile range [IQR] 38-132) months, 41 recurrences (41%) and 31 deaths (31%) were confirmed. Patients with GTR/NTR had a median PFS of 41 (IQR 24-70) months. Patients with subtotal resection or biopsy had a median PFS of 38 (IQR 16-97) months. The median PFS of patients who received radiation therapy was 43 (IQR 26-86) months, while that of patients who did not receive radiation therapy was 18 (IQR 5-62) months. The Kaplan-Meier method showed that patients with GTR/NTR (p = 0.007) and those who received radiation therapy (p < 0.001) had longer PFS than their counterparts. The PFS rates following primary treatment at 5, 10, 15, and 20 years were 51%, 25%, 17%, and 7%, respectively. The OS rates at the same intervals were 84%, 60%, 42%, and 34%, respectively. Multivariate Cox regression analysis showed that age < 44 years (p = 0.02), greater extent of resection (EOR; p = 0.03), and radiation therapy (p < 0.001) were associated with lower recurrence rates. Another multivariate analysis showed that age < 44 years (p = 0.01), greater EOR (p = 0.04), and freedom from recurrence (p = 0.02) were associated with lower mortality rates. Regarding pathology data, brachyury was positive in 98%, pan-cytokeratin in 93%, epithelial membrane antigen in 85%, and S100 in 74%. No immunohistochemical markers were associated with recurrence. CONCLUSIONS: In this study, younger age, maximal safe resection, and radiation therapy were important factors for longer PFS in patients with primary clival chordomas. Preventing recurrences played a crucial role in achieving longer OS.

Fluorescein-guided surgery in high-grade gliomas: focusing on the eloquent and deep-seated areas.

PURPOSE: The vital function of eloquent and deep brain areas necessitates precise treatment for tumors located in these regions. Fluorescein-guided surgery (FGS) has been widely used for high-grade gliomas (HGGs) resection. Nevertheless, the safety and efficacy of utilizing this technique for resecting brain tumors located in eloquent and deep-seated areas remain uncertain. This study aims to assess the safety and extent of resection of HGGs in these challenging tumors with fluorescein and explore its impact on patient survival. METHODS: A retrospective analysis was conducted on the clinical and radiological data of 67 consecutive patients with eloquent or deep-seated HGGs who underwent surgery between January 2020 and June 2023. Lacroix functional location grade was used to determine the eloquence of the tumors. The comparison between the fluorescence-guided surgery group (FGS, n = 32) and the conventional white-light microscopic surgery group (non-FGS, n = 35) included assessments of extent of resection (EOR), rates of gross total resection (GTR, 100%) and near-total resection (NTR, 99 to 98%), postoperative Neurologic Assessment in Neuro-Oncology (NANO) scores, overall survival (OS), and progression-free survival (PFS), to evaluate the safety and efficacy of fluorescein-guided technology in tumor resection at these specific locations. RESULTS: Baseline of demographics, lesion location, and pathology showed no significant difference between the two groups. GTR of the FGS group was higher than the non-FGS group (84.4% vs. 60.0%, OR 3.60, 95% CI 1.18-10.28, p < 0.05). The FGS group also showed higher GTR + NTR (EOR ≥ 98%) than the non-FGS group (93.8% vs. 65.7%, OR 7.83, 95% CI 1.86-36.85, p < 0.01). 87.0% of eloquent tumors (Lacroix grade III) in the FGS group achieved GTR + NTR, compared to 52.2% of control group (OR 6.11, 95% CI 1.50-22.78, p < 0.05). For deep-seated tumors, the rate of GTR + NTR in the two groups were 91.7% and 53.3%, respectively (OR 9.62, 95% CI 1.05-116.50, p < 0.05). No significant difference of the preoperative NANO score of the two groups was found. The postoperative NANO score of the FGS group was significantly lower than the non-FGS group (2.56 ± 1.29 vs. 3.43 ± 1.63, p < 0.05). Median OS of the FGS group was 4.2 months longer than the non-FGS group despite no statistical difference (18.2 months vs. 14.0 months, HR 0.63, 95% CI 0.36-1.11, p = 0.112), while PSF was found significantly longer in FGS patients than those of the non-FGS group (11.2 months vs. 7.7 months, HR 0.59, 95% CI 0.35-0.99, p < 0.05). CONCLUSION: Sodium fluorescein-guided surgery for high-grade gliomas in eloquent and deep-seated brain regions enables more extensive resection while preserving neurologic function and improve patient survival.

Radical surgical resection with molecular margins is associated with improved survival in IDH wildtype GBM.

BACKGROUND: Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically-detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of post-surgical progressive events are failures within 2cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown. METHODS: We developed a predictive model to identify which IDH wild-type GBM are amenable to radiographic gross total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden a by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation. RESULTS: Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an AUC of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found 89% of patients were correctly predicted to achieve a RV<4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a gross total resection (RV<1cc). In these 5 patients at 30 months follow up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (p=0.02). CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefit from radical resection to undetectable molecular margins.

Single versus multiple reoperations for recurrent intracranial meningiomas.

PURPOSE: To identify the risk factors and management of the multiple recurrences and reoperations for intracranial meningiomas. METHODS: Data of a neurosurgical series of 35 patients reoperated on for recurrent intracranial meningiomas were reviewed. Analyzed factors include patient age and sex, tumor location, extent of resection, WHO grade, Ki67-MIB1 and PR expression at initial diagnosis, time to recurrence; pattern of regrowth, extent of resection, WHO grade and Ki67-MIB1 at first recurrence were also analyzed. All these factors were stratified into two groups based on single (Group A) and multiple reoperations (Group B). RESULTS: Twenty-four patients (69%) belonged to group A and 11 (31%) to group B. The age < 65 years, male sex, incomplete resection at both initial surgery and first reoperation, and multicentric-diffuse pattern of regrowth at first recurrence are risk factors for multiple recurrences and reoperations. In group B, the WHO grade and Ki67-MIB1 increased in further recurrences in 54% and 64%, respectively. The time to recurrence was short in 7 cases (64%), whereas 4 patients (36%) further recurred after many years. Eight patients (73%) are still alive after 7 to 22 years and 2 to 4 reoperations. CONCLUSION: The extent of resection and the multicentric-diffuse pattern of regrowth at first recurrence are the main risk factors for multiple recurrences and reoperations. Repeated reoperations might be considered even in patients with extensive recurrent tumors before the anaplastic transformation occurs. In such cases, even partial tumor resections followed by radiation therapy may allow long survival in good clinical conditions.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma.

OBJECTIVE: Complete resection of malignant gliomas is often challenging. Our previous study indicated that intraoperative contrast-enhanced ultrasound (ICEUS) could aid in the detection of residual tumor remnants and the total removal of brain lesions. This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma. METHODS: A total of 64 patients diagnosed with malignant glioma (WHO grade HI and IV) who underwent surgery between 2012 and 2018 were included. Among them, 29 patients received ICEUS. The effects of ICEUS on overall survival (OS) and progression-free survival (PFS) of patients were evaluated. A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues. RESULTS: The ICEUS group showed better survival rates both in OS and PFS than the control group. The univariate analysis revealed that age, pathology and ICEUS were significant prognostic factors for PFS, with only age being a significant prognostic factor for OS. In multivariate analysis, age and ICEUS were significant prognostic factors for both OS and PFS. The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue. CONCLUSION: ICEUS facilitates the identification of residual tumors. Age and ICEUS are prognostic factors for malignant glioma surgery, and use of ICEUS offers a better prognosis for patients with malignant glioma.

Single brain metastases - prognostic factors and impact of residual tumor burden on overall survival.

Background: Brain metastases (BM) are a common and challenging issue, with their incidence on the rise due to advancements in systemic therapies and increased patient survival. Most patients present with single BM, some of them without any further extracranial metastasis (i.e., solitary BM). The significance of postoperative intracranial tumor volume in the treatment of singular and solitary BM is still debated. Objective: This study aimed to determine the impact of resection and postoperative tumor burden on overall survival (OS) in patients with single BM. Methods: Patients with surgically treated single BM between 04/2007-01/2020 were retrospectively included. Residual tumor burden (RTB) was determined by manual segmentation of early postoperative brain MRI (72 h). Survival analyses were performed using Kaplan-Meier estimates for univariate analysis and Cox regression proportional hazards model for multivariate analysis, using preoperative Karnofsky performance status scale (KPSS), age, sex, RTB, incomplete resection and singular/solitary BM as covariates. Results: 340 patients were included, median age 64 years (54-71). 119 patients (35%) had solitary BM, 221 (65%) singular BM. Complete resection (RTB=0) was achieved in 73%, median preoperative tumor burden was 11.2 cm3 (5-25), and RTB 0 cm3 (0-0.2). Median OS of patients with singular BM was 13 months (4-33) vs 20 months (5-92) for solitary BM; p=0.062. Multivariate analysis revealed singular BM as independent risk factor for poorer OS: HR 1.840 (1.202-2.817), p=0.005. Complete vs. incomplete resection showed no significant OS difference (13 vs. 13 months, p=0.737). When focusing on solitary BM, complete resection led to a longer OS than incomplete resection (21 vs. 8 months), without statistical significance(p=0.250). Achieving RTB=0 resulted in higher OS for patients with solitary BM compared to singular BM (21 vs. 12 months, p=0.027). Patients who received postoperative radiotherapy (RT) had significantly longer OS compared to those without it (14 vs. 4 months, p<0.001), with favorable OS in those receiving stereotactic radiosurgery (SRS) (15 months (3-42), p<0.001) or hypofractionated stereotactic radiotherapy (HSRT). Conclusion: When complete intracranial tumor resection RTB=0 is achieved, patients with solitary BM have a favorable outcome compared to singular BM. Singular BM was confirmed as independent risk factor. There is a strong presumption that complete resection leads to an improved oncological prognosis. Patients with solitary BM tend to benefit with a favorable outcome following complete resection. Hence, surgical resection should be considered as a treatment option for patients presenting with either no or minimal extracranial disease. Furthermore, the highly favorable impact of postoperative RT on OS was demonstrated and confirmed, especially with SRS or HSRT.

Evaluation of the extent of resection of intracranial tumors with virtual intraoperative MRI: a case series.

OBJECTIVE: Intraoperative MRI (iMRI) is the gold-standard technique for intraoperative evaluation of the extent of resection in brain tumor surgery. Unfortunately, it is currently available at only a few neurosurgical centers. A commercially available software, Virtual iMRI Cranial, provides an elastic fusion between preoperative MRI and intraoperative CT (iCT). The aim of this study was to evaluate the accuracy of this software in determining the presence of residual tumor. METHODS: Virtual iMRI was performed in patients who underwent iCT after intracranial tumor resection. The results of the software in terms of presence or absence of tumor residual were then compared with postoperative MRI performed within 48 hours after surgery to evaluate the diagnostic accuracy of virtual iMRI. RESULTS: Sixty-six patients were included in the present study. The virtual iMRI findings were concordant with the postoperative MRI data in 35 cases (53%) in the detection of tumor residual (p = 0.006). No false-negative findings (i.e., presence of residual on postoperative MRI and absence of residual on virtual iMRI) were encountered. Virtual iMRI had a sensitivity of 1 (95% CI 0.86-1), specificity of 0.26 (95% CI 0.14-0.42), positive predictive value of 0.44 (95% CI 0.3-0.58), and negative predictive value of 1 (95% CI 0.72-1). Subgroup analysis revealed that the virtual iMRI findings were concordant with postoperative MRI findings in all cases (n = 9) of lower-grade glioma (LGG) with a sensitivity of 1 (95% CI 0.59-1) and a specificity of 1 (95% CI 0.16-1) (p = 0.003); a statistically significant association was also found for grade 4 gliomas with a sensitivity of 1 (95% CI 0.69-1) and a specificity of 0.33 (95% CI 0.08-0.7) (p = 0.046) (19 patients). No significant association was found when considering meningiomas or metastases. CONCLUSIONS: The commercially available virtual iMRI can predict the presence or absence of tumor residual with high sensitivity. The diagnostic accuracy of this method was higher in LGGs and much lower for meningiomas or metastases; these findings must be evaluated in prospective studies in a larger population.

Predictors of Progression in a Series of 81 Adult Patients Surgically Managed for an Intracranial Hemangioblastoma: Implications for the Postoperative Follow-Up.

The aim was to identify predictors of progression in a series of patients managed for an intracranial hemangioblastoma, in order to guide the postoperative follow-up modalities. The characteristics of 81 patients managed for an intracranial hemangioblastoma between January 2000 and October 2022 were retrospectively analyzed. The mean age at diagnosis was of 48 ± 16 years. Eleven (14%) patients had von Hippel-Lindau disease. The most frequent tumor location was the cerebellar hemispheres (n = 51, 65%) and 11 (14%) patients had multicentric hemangioblastomas. A gross total resection was achieved in 75 (93%) patients. Eighteen (22%) patients had a local progression, with a median progression-free survival of 56 months 95% CI [1;240]. Eleven (14%) patients had a distant progression (new hemangioblastoma and/or growth of an already known hemangioblastoma). Local progression was more frequent in younger patients (39 ± 14 years vs. 51 ± 16 years; p = 0.005), and those with von Hippel-Lindau disease (n = 8, 44% vs. n = 3, 5%, p < 0.0001), multiple cerebral locations (n = 3, 17% vs. n = 2, 3%, p = 0.02), and partial tumoral resection (n = 4, 18% vs. n = 1, 2%, p = 0.0006). Therefore, it is advisable to propose a postoperative follow-up for at least 10 years, and longer if at least one predictor of progression is present.